A correlation was found between the antagonistic effects of cAMP and estrogen on nuclear protein phosphorylation in vitro and the hormone-dependency of mammary tumor growth in vivo. The antagonistic action between cAMP and estrogen was further revealed on the phosphorylation of the 56,000-dalton cAMP binding protein in the cytoplasm of hormone-dependent tumors, suggesting a close relation between the phosphorylation of cAMP binding protein and phosphorylation of nuclear proteins. These results provide further support for our initial proposal that the growth control of hormone-dependent mammary tumors is dependent on the interaction of cAMP and estrogen.